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Understanding Japanese Encephalitis in the Context of Travel Medicine

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 15th Conference of the International Society of Travel Medicine

Barcelona, Spain / May 14-18, 2017

Barcelona - Japanese encephalitis is caused by a mosquito-borne flavivirus, predominant in Asian countries, belonging in the same genus as the dengue, yellow fever, West Nile and Zika viruses.1,2 Even though the incidence is very low, and in most cases infection is mild, the case-fatality rate can be as high as 30%.1,3 Children are most commonly affected, and it is thought that adults in endemic areas may have natural immunity.1 The risks and impact of the infection to travelers were recently discussed at a symposium at the 15th Conference of the International Society of Travel Medicine. There is no antiviral treatment for patients, any therapy is to manage symptoms and stabilize the patient.1 The infection is vaccine-preventable and environmental precautions are also possible. During the symposium, healthcare professionals were urged to consider several risk factors when counseling travelers before their trips abroad.

“We know that Japanese encephalitis is one of the more rare infections among travelers but it is one of the very severe ones, with a high case mortality rate, and also with a high proportion of patients with remaining sequelae”, said Dr. Robert Steffen (Epidemiology, Biostatistics and Prevention Institute, WHO Collaborating Centre for Travelers’ Health, University of Zurich, Zurich, Switzerland) as he opened this symposium during the sanctioned scientific sessions.

Background, Epidemiology and Clinical Manifestation

The principal vector of Japanese encephalitis is mosquitos from the Culex genus, mainly Culex tritaeniorhynchus, also known as the night-time biting mosquito. There is greater risk of infection in rural areas, regions with high rainfall and rice fields, explained Dr. Pornthep Chanthavanich (Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Thailand) in his talk. The virus is maintained in a cycle between mosquitos and vertebrate hosts, mainly pigs and wading birds with humans being dead-end hosts, and the last in the cycle being unable to transmit the infection.4

Current data show that there are about 60,000 cases in 24 endemic countries in Asia and parts of Australia. With an overall incidence of 1.8 per 100,000”, said Dr. Chanthavanich.

Dr. Tomas Jelinek (Berlin Center for Travel and Tropical Medicine, Berlin, Germany and Institute of Medical Microbiology, Immunology and Hygiene, University of Cologne, Germany) addressed the likelihood of infection among travelers in his talk in the session. “So how do you assess the risk when counseling the traveler? Obviously it is a rare risk and a rare disease in travelers, there is no doubt about that. But it is very difficult to assess the exact incidence in travelers. Swedish data says it’s about 1 case per 400,000 trips and other data says about 1.3 cases per 7.1 million visits, among 17 million European travelers.”

Less than 1% of people infected with Japanese encephalitis develop clinical illness.4 The incubation period can be between 5 and 15 days, said Dr. Chanthavanich, and illness has three main stages. The prodromal stage includes initial symptoms of fever, headache and vomiting. The second stage is known as the acute encephalitis stage and includes neurological involvement, convulsions, and coma. In mild to moderate cases these symptoms might improve after 1-2 weeks but in severe cases there can be complications. And then the final stage: convalescent stage, which can be after 4-7 weeks after the start of symptoms.6

Most cases of Japanese encephalitis are mild (with fever and headache) or without apparent symptoms but approximately one in 250 infections result in severe clinical illness.1

There is a noticeable difference between indigenous and non-indigenous adults--one study found that US Marines that were stationed in Thailand in the 1970s, had a higher rate of symptomatic disease compared with the local population.5

“Those with poor prognosis usually have a short prodromal interval, are comatosed on admission and may suffer uncontrolled convulsions, respiratory dysfunction, prolonged fever, focal presentation and presence of extrapyramidal tract signs or pathological reflexes”, said Dr. Chanthavanich at the end of this talk.

Impact on Patients

Dr. Ava Easton, PhD, Chief Executive, The Encephalitis Society discussed the impact of the disease on patients and their families by pointing to three patients who contracted the infection on their travels in Asia. Outcomes can range from good recovery, mild disability to moderate to severe outcomes, such as vegetative state to death, explained Dr. Easton. When discussing these cases she talked of one young patient who made a good recovery but still suffers with mild cognitive problems with particular difficulties with memory and fatigue after 3 years of contracting the infection. Another young patient (31 years) contracted the infection in China a couple of years ago while working as a research conservationist and is now paralysed from the waist up and still being managed in the high dependency unit.

She urged practitioners to consider that even though a destination may have a low incidence, people may travel beyond their original itineraries. Dr. Easton also noted that when speaking to these patients and their families that they were told about likelihood of the disease but not severity or impact in particular.

Understanding the Risk

There are factors that may impact likelihood of infection, said Dr. Bradley Connor (Weill Cornell Medical College and The New York Center for Travel and Tropical Medicine), such as old age. “The risk of neuroinvasive disease is 5 to 10 fold times higher in people aged 50 years and older.” He also stated that young age is also a risk for symptomatic disease and is associated with high frequency of neurological sequelae. Other factors he points out are immunodeficiency, which has been associated with an increased risk of flavivirus infections, and pregnancy.

Dr. Connor goes onto question whether the current recommendations are sufficient for practitioners’ decision-making regarding immunization. The World Health Organization advises that all travelers going to endemic areas should take precautions to avoid mosquito bites and reduce the risk of Japanese encephalitis with repellents, clothes, coils and vaporizers.1 Travelers spending extensive time in endemic areas are advised to get vaccinated.1 There are four main types of vaccine for Japanese encephalitis currently in use including inactivated mouse brain-derived vaccines, inactivated Vero cell-derived vaccines, live attenuated vaccines, and live recombinant vaccines.1 The US Centers for Disease Control recommends the inactivated Vero cell culture-derived Japanese encephalitis vaccine (manufactured as IXIARO by Valneva) for travelers who plan to spend 1 month or more in endemic areas during the virus transmission season. The vaccine should also be considered for short-term travelers who plan to travel outside of urban areas and if their activities will increase the risk of virus exposure.

In his talk Dr. Jelinek looked at assessing the risk among travelers as he pointed out that were a few cases of Japanese encephalitis that did not fit within these constraints, with some patients contracting the infection in beach resorts or within a short two-week holiday.

“We have also heard of cases occurring outside of the expected transmission season, in places like urban areas, which used to be considered no risk areas,” said Dr. Bradley Connor in his talk. “So what do these case studies in Western travelers tell us? Different types of travelers have been affected by Japanese encephalitis and it is difficult to clearly define and exceptions frequently occur.”

Seasonality

The World Health Organization states that transmission of Japanese encephalitis intensifies during the rainy season, during which vector populations increase.1 But Dr. Jelinek questioned in his talk whether there was actually a correlation between the rainy season and rate of infection. Pointing to a 2009 study where 11 cases of travelers in Thailand were reviewed, he noted that the disease did not seem to be associated with seasons of high risk and length of stay.7 “Most of the cases did not correlate with the rainfall”, said Dr. Jelinek. “Obviously behavior and destination in cases offer no clear pattern so it is difficult to state the risk in advance. Japanese encephalitis epidemics are totally unpredictable occurring in both rainy seasons and dry seasons.”

Advising Patients

Personal protection methods are recommended, said Dr. Connor . But he went onto explain that the Culex mosquito most commonly bites at sundown, dusk and throughout the night and early morning hours. Bednets and barrier protection only partially protects, he said, “human vaccination is the best protection”.

He said when counseling travelers location, duration of trip, activities and the season must be considered. As well as the traveler’s attitude to risk taking. “We need to think about the likelihood of contracting this disease versus the severity of the disease, and this is one of those diseases that is a potential risk to travelers and can have a devastating consequence”. In conclusion, it is important to have a discussion about Japanese encephalitis and how to minimize the risk with travelers to endemic countries in Asia.

 

References

1. World Health Organization. Japanese encephalitis fact sheet. 2015 Available at: http://www.who.int/mediacentre/factsheets/fs386/en/  2. Centers for Disease Control and Prevention. Zika. 2016. Available at: https://www.cdc.gov/zika/hc-providers/preparing-for-zika/clinicalevaluationdisease.html  3. World Health Organization. Immunization, Vaccines and Biologicals: Japanese encephalitis. http://www.who.int/immunization/diseases/japanese_encephalitis/en/  4. Centers for Disease Control and Prevention. Japanese encephalitis. 2015. Available at: https://www.cdc.gov/japaneseencephalitis/index.html  5. Benenson MW, Franklin HT Jr, Gresso W, et al. The virulence to man of Japanese encephalitis virus in Thailand. Am J Trop Med Hyg 1975; 24: 974-980.   6. Kumar R. Prevention, diagnosis and management of Japanese encephalitis in children. Pediatric Health Med Ther 2014; 5: 99-110.   7. Bhul MR, Lindquist L. Japanese encephalitis in travelers: review of cases and seasonal risk. J Travel Med 2009; 16: 217-219.

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